Three types of opioid receptors, i.e., μ, δ, and κ receptors, are known, and morphine showing potent affinity to the μ receptor has been used as an analgesic for a long time. Although morphine has potent analgesic effect, it is known that morphine causes adverse events such as formation of dependence, respiratory depression, and constipation via the μ receptor.
It is further known that, although the δ receptor also has an analgesic action, δ receptor agonists are not involved in the adverse events observed for morphine.
Therefore, it is considered that a δ receptor-selective agonist may have a potential as an analgesic superior to morphine, and for this reason, researches concerning creation of such an analgesic have been actively conducted. It is also reported that a δ receptor agonist may serve as an antianxiety drug or antidepressant (Non-patent documents 1, 2, 3, 4, and 5).
However, any δ receptor agonist has not been approved yet as a therapeutic or prophylactic agent.
Patent document 1 describes that the compound represented by the following formula (A):
has an opioid δ receptor agonistic activity.
Further, in Non-patent document 6, the inventors of the present invention made reports concerning the compound represented by the following formula (B).
However, this compound has higher affinity to the μ receptor than the δ receptor.
The inventors of the present invention recently also found that the compound represented by the following formula (C):
in which the morphinan structure is cyclized at the 4- and 6-positions via a methylenedioxy structure, has a 6 against activity, and filed a patent application therefor (Patent document 2).